The present invention relates to a tracheobronchodilator containing 15-keto-prostaglandin E and their derivatives. In the present specification a series of prostaglandins and their derivatives is abbreviated to PGs. Accordingly, a series of compounds belonging to 15-keto-prostaglandin E such as 15-keto-prostaglandin E.sub.1, E.sub.2, esters, salts, or others having substituents is generically called 15-keto-PGEs. Term "PGE.sub.1 s" means a series of compounds belonging to PGE.sub.1.
Prostaglandin is a generic name of one kind of carboxylic acids having a variety of physiological activities, which are found in tissues or internal organs of humans or animals. PGs have a basic skeleton of a prostanoic acid represented by following formula: ##STR1## There have been provided various kinds of synthetic PGs modified on one or more carbon atom(s) of the skeleton.
PGs are classified into PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGIs, and PGJs and so on according to the structure of the five members ring in the above skeleton. Further, they are classified into PG.sub.1 s in which the bond between 5- and 6-positions is a single bond; PG.sub.2 s in which the bond between 5- and 6-positions is a double bond; and PG.sub.3 s in which the bonds between 5- and 6-positions, and between 17- and 18-positions are double bonds respectively. These PGs have a double bond between 13- and 14-position and a hydroxyl group on 15-position.
PGs exhibit various kinds of pharmacological and physiological activity. For instance, it has been known that PGE.sub.1 s, PGE.sub.2 s and the like have a tracheobronchodilation which also have side effects such as enterocontraction, intraocular hypertension, and especially stimuli against bronchi.
There have been also found of PGEs in metabolites of animals or humans, in which the bond between 13- and 14-positions is a single bond (saturated) and the carbon atom of 15-position forms a carbonyl group; or in which the bond between 13- and 14-positions is a double bond and the carbon atom of 15-position constitutes a carbonyl group.
15-keto-prostaglandin E (noted as 15-keto-PGE hereinafter) and 13,14-dihydro-15-keto-prostaglandin E (noted as 13,14-dihydro-15-keto-PGE hereinafter) are known as a substance naturally produced by an enzyme in the metabolism of prostaglandin E (noted as PGE hereinafter) in a living body. These 15-keto-PGE have been considered to be physiologically and pharmacologically inactive substances (Acta Physiologica Scandinavica, Vol. 66, pp509 (1966)). It has never been recognized that these 15-keto-PGE have tracheobronchodilation activity.